PEPD Gene (Peptidase D)
Prolidase Deficiency and Collagen Metabolism
Gene Information Card
| Symbol | PEPD |
|---|---|
| Full Name | Peptidase D |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.11 |
| NCBI Gene ID | 5184 ncbi.nlm.nih.gov/gene/5184 |
| Ensembl ID | ENSG00000105699 |
| UniProt ID | P12955 |
| OMIM ID | 613230 |
| HGNC ID | 8840 |
| Aliases | PROLIDASE, PEPD1 |
Description
The PEPD gene encodes prolidase, a cytosolic dipeptidase that specifically cleaves imidodipeptides containing a proline or hydroxyproline residue at the C-terminus. This enzyme is critical for the recycling of proline from collagen degradation products, thereby playing a key role in collagen metabolism and connective tissue homeostasis. Mutations in PEPD cause prolidase deficiency, an autosomal recessive disorder characterized by skin ulcers, intellectual disability, and characteristic facies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prolidase Deficiency | Loss-of-function mutations in PEPD reduce or abolish prolidase activity, leading to accumulation of imidodipeptides and impaired collagen recycling. This results in connective tissue fragility, skin lesions, and neurological symptoms. | Multiple case reports and functional studies (OMIM #170100) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Liver | 10.2 | Medium |
| Small Intestine | 8.9 | Medium |
| Lung | 6.3 | Low |
| Heart | 5.1 | Low |
| Brain | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.0 | High expression in kidney-derived line |
| HepG2 | 11.5 | Moderate expression in liver line |
| A549 | 7.2 | Low expression in lung line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1342C>T (p.Arg448*) | Nonsense | Rare | Premature stop, loss of function |
| c.794G>A (p.Gly265Asp) | Missense | Rare | Reduced enzyme activity |
| c.1022_1023del (p.Leu341Profs*12) | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most PEPD mutations cause loss of prolidase activity, leading to prolidase deficiency.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • Prolidase activity (GO:0016805) | • Dipeptidase activity (GO:0016805) |
| • Collagen catabolic process (GO:0030574) | • Proline metabolic process (GO:0006568) |
| • Cytosol (GO:0005829) |
Pathways
• ['Reactome'
• 'Collagen degradation (R-HSA-1442490)']
• ['KEGG'
• 'Arginine and proline metabolism (hsa00330)']
Protein Summary
Prolidase is a homodimeric cytosolic enzyme of approximately 54 kDa per subunit. It requires manganese ions for activity and specifically hydrolyzes dipeptides with a C-terminal proline or hydroxyproline. The enzyme is essential for the final step of collagen breakdown, allowing proline to be recycled for new protein synthesis. Deficiency leads to prolidase deficiency syndrome.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PEPD Knockout HEK293 Cell Line | EDJ-KQ5435 | Human | 5184 | Details Get a Quote |
| PEPD Knockout A-549 Cell Line | EDJ-KQ28612 | Human | 5184 | Details Get a Quote |
| PEPD Knockout HCT 116 Cell Line | EDJ-KQ28613 | Human | 5184 | Details Get a Quote |
| PEPD Knockout HeLa Cell Line | EDJ-KQ28614 | Human | 5184 | Details Get a Quote |
